title: Rapid desensitization and resensitization of 5-HT2 receptor mediated phosphatidyl inositol hydrolysis by serotonin agonists in quiescent calf aortic smooth muscle cells.
abstract: Agonist regulation of 5-hydroxytryptamine2 (5-HT2) receptors was studied in calf aortic smooth muscle cultures incubated in a quiescent, defined synthetic medium that does not stimulate cell proliferation, but that provides cells with supplements that maintain cell viability. In these cells, 5-hydroxytryptamine (5-HT)-induced [3H]inositol phosphates accumulation showed the characteristics of a 5-HT2 receptor coupled transducing system according to the inhibition of the response by 5-HT2 antagonists at nanomolar concentrations. The 5-HT2 receptor coupled response became rapidly desensitized during continued incubation with 5-HT and 1-(2,5-dimethoxy-4-methylphenyl)-2- aminopropane (DOM); nearly full desensitization was obtained in two hours with 10 microM 5-HT and DOM pretreatment. The recovery of the response had a half-live of 5 hours after 2 hours pretreatment and of 9.5 to 12.5 hours after 24 to 96 hours agonist pretreatment. The DOM-induced desensitization of the 5-HT2 receptor coupled response was fully blocked by 0.1 microM cinanserin. Cinanserin alone did not induce desensitization or up-regulation of the 5-HT2 receptor coupled response at 0.1 microM. It may be that the down-regulation of central 5-HT2 receptors by antagonists in vivo is a heterologous process due to mediators which are triggered by 5-HT2 antagonistic action.
authors.affiliation: Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium.
authors.forename: P J
authors.initials: PJ
authors.lastname: Pauwels
authors.forename: P
authors.initials: P
authors.lastname: Van Gompel
authors.forename: J E
authors.initials: JE
authors.lastname: Leysen
mesh_terms: D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D002928:Cinanserin / Q000494:pharmacology; D003470:Culture Media; D004361:Drug Tolerance; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D003470:Culture Media; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D012701:Serotonin; D002928:Cinanserin